Is Autologous Fat Grafting an Oncologically Safe Procedure following Breast Conserving Surgery for Breast Cancer? A Comprehensive Review.

BACKGROUND: Autologous fat grafting (AFG) is a recognized surgical procedure to correct deformities following breast conservation surgery (BCS) for breast cancer. However, there are concerns about the oncological safety of this technique. In this study we have reviewed the current literature to assess whether AFG adversely influences the oncological outcome after BCS for breast cancer. METHODS: We have searched the medical literature using the Embase and PubMed search engines from conception until May 2019 to identify all relevant studies of patients who underwent AFG after BCS. Meta-analysis and meta-regression methodologies were used to calculate the overall relative risk (RR) of loco-regional recurrence (LRR) rates for case-control and case series studies (with historical controls) respectively. RESULTS: We have identified 26 eligible studies with a total of 1640 patients who had undergone fat transfer after lumpectomy for breast cancer. The meta-analysis of 11 studies revealed an overall RR for LRR of 0.82 [95% confidence interval (CI):0.14-1.66]. The meta-regression of case series revealed an overall incidence of LRR of 1.85% compared with 2.53% for historical controls. CONCLUSIONS: Our study lends further support to the notion that fat transfer after lumpectomy for breast cancer does not seem to increase the risk of LRR. However further prospective research is required in order to confirm this.

A multicentre prospective feasibility study of carbon dye tattooing of biopsied axillary node and surgical localisation in breast cancer patients.

BACKGROUND: The primary aim of this prospective, multicentre feasibility study was to determine whether the biopsied axillary node can be marked using black carbon dye and successfully identified at the time of surgery. METHODS: We included breast cancer patients undergoing needle biopsy of the axillary node. The biopsied node was tattooed at the time of needle biopsy (fine needle aspiration or core biopsy) or at a separate visit with black carbon dye (Spot® or Black Eye™). Participants underwent primary surgery or neoadjuvant chemotherapy (NACT) and axillary surgery (SNB or ALND) as per routine care. RESULTS: 110 patients were included. Median age of the women was 59 (range 31-88) years. 48 (44%) underwent SNB and 62 (56%) ALND. Median volume of dye injected was 2.0 ml (range 0.2-4.2). Tattooed node was identified intra-operatively in 90 (82%) patients. The identification rate was higher (76 of 88, 86%) in the primary surgery group compared with NACT (14 of 22, 64%) (p = 0.03). Of those undergoing NACT, the identification rate was better in the patients undergoing SNB (3 of 4, 75%) compared with ALND (11 of 18, 61%) (p > 0.99). The tattooed node was the sentinel node in 78% (28 of 36) patients in the primary surgery group and 100% (3 of 3) in the NACT group. There was no learning curve for surgeons or radiologists. The identification rate did not vary with timing between dye injection and surgery (p = 0.56), body mass index (p = 0.62) or volume of dye injected (p = 0.25). CONCLUSION: It is feasible to mark the axillary node with carbon dye and identify it intra-operatively. ClinicalTrials.gov: NCT03640819.

Opportunities and priorities for breast surgical research.

The 2013 Breast Cancer Campaign gap analysis established breast cancer research priorities without a specific focus on surgical research or the role of surgeons on breast cancer research. This Review aims to identify opportunities and priorities for research in breast surgery to complement the 2013 gap analysis. To identify these goals, research-active breast surgeons met and identified areas for breast surgery research that mapped to the patient pathway. Areas included diagnosis, neoadjuvant treatment, surgery, adjuvant therapy, and attention to special groups (eg, those receiving risk-reducing surgery). Section leads were identified based on research interests, with invited input from experts in specific areas, supported by consultation with members of the Association of Breast Surgery and Independent Cancer Patients' Voice groups. The document was iteratively modified until participants were satisfied that key priorities for surgical research were clear. Key research gaps included issues surrounding overdiagnosis and treatment; optimising treatment options and their selection for neoadjuvant therapies and subsequent surgery; reducing rates of re-operations for breast-conserving surgery; generating evidence for clinical effectiveness and cost-effectiveness of breast reconstruction, and mechanisms for assessing novel interventions; establishing optimal axillary management, especially post-neoadjuvant treatment; and defining and standardising indications for risk-reducing surgery. We propose strategies for resolving these knowledge gaps. Surgeons are ideally placed for a central role in breast cancer research and should foster a culture of engagement and participation in research to benefit patients and health-care systems. Development of infrastructure and surgical research capacity, together with appropriate allocation of research funding, is needed to successfully address the key clinical and translational research gaps that are highlighted in this Review within the next two decades.

Downregulation of aquaporin 3 inhibits cellular proliferation, migration and invasion in the MDA-MB-231 breast cancer cell line.

Aquaporins are membrane proteins that regulate cellular water flow. Recently, aquaporins have been proposed as mediators of cancer cell biology. A subset of aquaporins, referred to as aquaglyceroporins are known to facilitate the transport of glycerol. The present study describes the effect of gene knockdown of the aquaglyceroporin AQP3 on MDA-MB-231 breast cancer cell proliferation, migration, invasion, adherence and response to the chemotherapeutic agent 5-fluorouracil. shRNA mediated AQP3 gene knockdown induced a 28% reduction in cellular proliferation (P<0.01), a 39% decrease in migration (P<0.0001), a 24% reduction in invasion (P<0.05) and a 25% increase in cell death at 100 µM 5-FU (P<0.01). Analysis of cell permeability to water and glycerol revealed that MDA-MB-231 cells with knocked down AQP3 demonstrated a modest decrease in water permeability (17%; P<0.05) but a more marked decrease in glycerol permeability (77%; P<0.001). These results suggest that AQP3 has a role in multiple aspects of breast cancer cell pathophysiology and therefore represents a novel target for therapeutic intervention.

Physical activity for women with breast cancer after adjuvant therapy.

BACKGROUND: Women with a diagnosis of breast cancer may experience short- and long-term disease and treatment-related adverse physiological and psychosocial outcomes. These outcomes can negatively impact prognosis, health-related quality of life (HRQoL), and psychosocial and physical function. Physical activity may help to improve prognosis and may alleviate the adverse effects of adjuvant therapy. OBJECTIVES: To assess effects of physical activity interventions after adjuvant therapy for women with breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform, on 18 September 2015. We also searched OpenGrey and Healthcare Management Information Consortium databases. SELECTION CRITERIA: We searched for randomised and quasi-randomised trials comparing physical activity interventions versus control (e.g. usual or standard care, no physical activity, no exercise, attention control, placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or radiation therapy, but not hormone therapy) in women with breast cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when needed. We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome and used GRADE to assess the quality of evidence for the most important outcomes. MAIN RESULTS: We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic exercise and resistance training, and seven used resistance training only. Thirty studies described the comparison group as usual or standard care, no intervention, or control. One-fifth of studies reported at least 20% intervention attrition and the average physical activity adherence was approximately 77%.No data were available on effects of physical activity on breast cancer-related and all-cause mortality, or on breast cancer recurrence. Analysis of immediately postintervention follow-up values and change from baseline to end of intervention scores revealed that physical activity interventions resulted in significant small-to-moderate improvements in HRQoL (standardised mean difference (SMD) 0.39, 95% CI 0.21 to 0.57, 22 studies, 1996 women; SMD 0.78, 95% CI 0.39 to 1.17, 14 studies, 1459 women, respectively; low-quality evidence), emotional function (SMD 0.21, 95% CI 0.10 to 0.32, 26 studies, 2102 women, moderate-quality evidence; SMD 0.31, 95% CI 0.09 to 0.53, 15 studies, 1579 women, respectively; low-quality evidence), perceived physical function (SMD 0.33, 95% CI 0.18 to 0.49, 25 studies, 2129 women; SMD 0.60, 95% CI 0.23 to 0.97, 13 studies, 1433 women, respectively; moderate-quality evidence), anxiety (SMD -0.57, 95% CI -0.95 to -0.19, 7 studies, 326 women; SMD -0.37, 95% CI -0.63 to -0.12, 4 studies, 235 women, respectively; low-quality evidence), and cardiorespiratory fitness (SMD 0.44, 95% CI 0.30 to 0.58, 23 studies, 1265 women, moderate-quality evidence; SMD 0.83, 95% CI 0.40 to 1.27, 9 studies, 863 women, respectively; very low-quality evidence).Investigators reported few minor adverse events.Small improvements in physical activity interventions were sustained for three months or longer postintervention in fatigue (SMD -0.43, 95% CI -0.60 to -0.26; SMD -0.47, 95% CI -0.84 to -0.11, respectively), cardiorespiratory fitness (SMD 0.36, 95% CI 0.03 to 0.69; SMD 0.42, 95% CI 0.05 to 0.79, respectively), and self-reported physical activity (SMD 0.44, 95% CI 0.17 to 0.72; SMD 0.51, 95% CI 0.08 to 0.93, respectively) for both follow-up values and change from baseline scores.However, evidence of heterogeneity across trials was due to variation in intervention components (i.e. mode, frequency, intensity, duration of intervention and sessions) and measures used to assess outcomes. All trials reviewed were at high risk of performance bias, and most were also at high risk of detection, attrition, and selection bias. In light of the aforementioned issues, we determined that the evidence was of very low, low, or moderate quality. AUTHORS' CONCLUSIONS: No conclusions regarding breast cancer-related and all-cause mortality or breast cancer recurrence were possible. However, physical activity interventions may have small-to-moderate beneficial effects on HRQoL, and on emotional or perceived physical and social function, anxiety, cardiorespiratory fitness, and self-reported and objectively measured physical activity. The positive results reported in the current review must be interpreted cautiously owing to very low-to-moderate quality of evidence, heterogeneity of interventions and outcome measures, imprecision of some estimates, and risk of bias in many trials. Future studies with low risk of bias are required to determine the optimal combination of physical activity modes, frequencies, intensities, and durations needed to improve specific outcomes among women who have undergone adjuvant therapy.

The effects of a home-based physical activity intervention on cardiorespiratory fitness in breast cancer survivors; a randomised controlled trial.

The aim of this current randomised controlled trial was to evaluate the effects of a home-based physical activity (PA) intervention on cardiorespiratory fitness in breast cancer survivors. Thirty-two post-adjuvant therapy breast cancer survivors (age = 52 ± 10 years; BMI = 27.2 ± 4.4 kg∙m2) were randomised to a six-month home-based PA intervention with face-to-face and telephone PA counselling or usual care. Cardiorespiratory fitness and self-reported PA were assessed at baseline and at six-months. Participants had a mean relative V̇O2max of 25.3 ± 4.7 ml∙kg-1∙min-1, which is categorised as "poor" according to age and gender matched normative values. Magnitude-based inference analyses revealed likely at least small beneficial effects (effect sizes ≥.20) on absolute and relative V̇O2 max (d = .44 and .40, respectively), and total and moderate PA (d = .73 and .59, respectively) in the intervention compared to the usual care group. We found no likely beneficial improvements in any other outcome. Our home-based PA intervention led to likely beneficial, albeit modest, increases in cardiorespiratory fitness and self-reported PA in breast cancer survivors. This intervention has the potential for widespread implementation and adoption, which could considerably impact on post-treatment recovery in this population.

Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMend™) in implant based immediate reconstruction following skin sparing mastectomy: A prospective observational study in a single centre.

INTRODUCTION: The advent of acellular dermal matrix devices (ADMs) has enhanced both the scope of implant-based immediate breast reconstruction (IBR) following skin sparing mastectomy (SSM) for the treatment or risk reduction of breast cancer. Currently, there are a wide range of options available for the use of ADMs. METHODS: This is a prospective observational single institution study of 118 consecutive patients undergoing a total of 164 SSM and IBR procedures either for treatment for breast cancer or for risk reduction, between 2012 and 2014. IBR was performed using an implant and bovine-derived ADM (SurgiMend™). Nipple sparing mastectomy (NSM) accounted for 103 procedures. IBR was performed as a single stage procedure in 23% of patients. The primary endpoint of this prospective study was the explantation rate and secondary endpoints included quality of life, patient satisfaction, aesthetic outcome assessed objectively, surgical complications, overall and disease free survival. RESULTS: Forty-six patients (39%) had a bilateral and 72 underwent a unilateral SSM. Of those who underwent a unilateral SSM, 25 had a contralateral adjustment procedure. Out of 164 procedures, 117 (71%) were for the treatment of breast cancer. Sixty-one patients received chemotherapy (52%) and 32 (27%) had radiotherapy. In this study 27 patients underwent post-mastectomy radiotherapy. At a mean follow of 21 months, the explantation rate was 1.2%, 4% (6 patients) developed wound complications. The patient satisfaction with the procedure was found to be very high. The mean Breast Q Score was 85 and the mean overall patient satisfaction rating was 9 out of a possible 10. The mean objective assessment score was 8.9 out of a possible 10 and the mean subjective capsular contracture severity score was 2.9 out of 10. There were two cases of local recurrence (1.7%), one distant recurrence (0.8%) and one patient died of metastatic breast cancer (0.8%). Overall survival was 99.2% and locoregional disease free survival (LRFS) was 98.3%. One patient (0.8%) developed a mild inflammatory reaction secondary to the underlying mesh. CONCLUSIONS: SurgiMend™ is an effective adjunct to implant based IBR following SSM. It is associated with a very low rate of implant loss and a high level of patient satisfaction and is associated with a very low incidence of inflammatory reaction. Neither prior radiotherapy nor post-mastectomy radiotherapy (PMRT) represents a contraindication to its use.

Randomised controlled trial of a home-based physical activity intervention in breast cancer survivors.

BACKGROUND: To improve adherence to physical activity (PA), behavioural support in the form of behavioural change counselling may be necessary. However, limited evidence of the effectiveness of home-based PA combined with counselling in breast cancer patients exists. The aim of this current randomised controlled trial with a parallel group design was to evaluate the effectiveness of a home-based PA intervention on PA levels, anthropometric measures, health-related quality of life (HRQoL), and blood biomarkers in breast cancer survivors. METHODS: Eighty post-adjuvant therapy invasive breast cancer patients (age = 53.6 ± 9.4 years; height = 161.2 ± 6.8 cm; mass = 68.7 ± 10.5 kg) were randomly allocated to a 6-month home-based PA intervention or usual care. The intervention group received face-to-face and telephone PA counselling aimed at encouraging the achievement of current recommended PA guidelines. All patients were evaluated for our primary outcome, PA (International PA Questionnaire) and secondary outcomes, mass, BMI, body fat %, HRQoL (Functional assessment of Cancer Therapy-Breast), insulin resistance, triglycerides (TG) and total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol were assessed at baseline and at 6-months. RESULTS: On the basis of linear mixed-model analyses adjusted for baseline values performed on 40 patients in each group, total, leisure and vigorous PA significantly increased from baseline to post-intervention in the intervention compared to usual care (between-group differences, 578.5 MET-min∙wk(-1), p = .024, 382.2 MET-min∙wk(-1), p = .010, and 264.1 MET-min∙wk(-1), p = .007, respectively). Both body mass and BMI decreased significantly in the intervention compared to usual care (between-group differences, -1.6 kg, p = .040, and -.6 kg/m(2), p = .020, respectively). Of the HRQoL variables, FACT-Breast, Trial Outcome Index, functional wellbeing, and breast cancer subscale improved significantly in the PA group compared to the usual care group (between-group differences, 5.1, p = .024; 5.6, p = .001; 1.9 p = .025; and 2.8, p = .007, respectively). Finally, TC and LDL-C was significantly reduced in the PA group compared to the usual care group (between-group differences, -.38 mmol∙L(-1), p = .001; and -.3 mmol∙L(-1), p = .023, respectively). CONCLUSIONS: We found that home-based PA resulted in significant albeit small to moderate improvements in self-reported PA, mass, BMI, breast cancer specific HRQoL, and TC and LDL-C compared with usual care. CLINICALTRIALS. GOV IDENTIFIER: NCT02408107 (March 25, 2015).

Physical activity and awareness in breast screening attendees in Black Country, UK.

This study aimed to determine the physical activity levels and awareness of the influence of physical activity and overweight/obesity on breast cancer risk among NHS breast screening programme (NHSBSP) attendees. One hundred and eighty-eight (white British = 95%; post-menopausal = 80%) attendees completed a demographic and anthropometric data questionnaire, International Physical Activity Questionnaire (IPAQ) and awareness of breast cancer risk factors questionnaire. IPAQ data were reported as continuous measures (MET-min · week(-1)) and as categorical variables (low, moderate and high activities). The highest median physical activity levels were reported in the domestic physical activity domain (756 MET-min · week(-1)). Most participants were categorized as 'moderately active' (45%), while 30% were classified in the 'high activity' and 25% as 'low activity' categories. Almost a third of participants (30%) reported no leisure-time physical activity and 83% reported no vigorous physical activity. There was high awareness of the effects of physical activity (75%) and obesity (80%) on breast cancer risk. No significant differences were found between physical activity categories and awareness that physical activity can reduce breast cancer risk (p > 0.05). However, compared with moderate and high activity categories, participants in the 'low activity' category were significantly more likely to respond that they thought they achieved recommended physical activity levels (p < 0.05). Participants who are unaware of their inadequate physical activity levels may have a less positive intention to increase physical activity levels. Practical strategies aimed to increase knowledge of the recommended physical activity guidelines and facilitate the achievement of these guidelines may be required for NHSBSP attendees.

Breast cancer therapy and cardiovascular risk: focus on trastuzumab.

Breast cancer is the most common cancer in the UK. Advances in the methods of early diagnosis as well as newer and more effective treatments have led to improvements of disease-free and overall survival over the last decade. Almost one-third of breast cancers present with an aggressive form characterized by increased expression of human epidermal growth receptor 2 (HER2) proteins. A targeted treatment using monoclonal antibodies against HER2 expression such as trastuzumab has been shown to improve survival. Unfortunately, there is a degree of cardiotoxicity associated with these agents, as inhibition of HER2 pathways can also impair cardioprotective pathways. In the present review, we discuss the mechanisms by which trastuzumab might affect vascular homeostasis leading to endothelial dysfunction. We also provide suggestions for future research examining the effects of trastuzumab on the vasculature in breast cancer.

Evaluating the evidence for targeting FOXO3a in breast cancer: a systematic review.

BACKGROUND: Tumour cells show greater dependency on glycolysis so providing a sufficient and rapid energy supply for fast growth. In many breast cancers, estrogen, progesterone and epidermal growth factor receptor-positive cells proliferate in response to growth factors and growth factor antagonists are a mainstay of treatment. However, triple negative breast cancer (TNBC) cells lack receptor expression, are frequently more aggressive and are resistant to growth factor inhibition. Downstream of growth factor receptors, signal transduction proceeds via phosphatidylinositol 3-kinase (PI3k), Akt and FOXO3a inhibition, the latter being partly responsible for coordinated increases in glycolysis and apoptosis resistance. FOXO3a may be an attractive therapeutic target for TNBC. Therefore we have undertaken a systematic review of FOXO3a as a target for breast cancer therapeutics. METHODS: Articles from NCBI were retrieved systematically when reporting primary data about FOXO3a expression in breast cancer cells after cytotoxic drug treatment. RESULTS: Increased FOXO3a expression is common following cytotoxic drug treatment and is associated with apoptosis and cell cycle arrest. There is some evidence that metabolic enzyme expression is also altered and that this effect is also elicited in TNBC cells. FOXO3a expression serves as a positive prognostic marker, especially in estrogen (ER) receptor positive cells. DISCUSSION: FOXO3a is upregulated by a number of receptor-dependent and -independent anti-cancer drugs and associates with apoptosis. The identification of microRNA that regulate FOXO3a directly suggest that it offers a tangible therapeutic target that merits wider evaluation.

Heparanase and COX-2 expression as predictors of lymph node metastasis in large, high-grade breast tumors.

BACKGROUND/AIM: Heparanase (HPA) contributes to breast cancer metastasis by facilitating the breakdown of the basement membrane and extracellular matrix. High expression of HPA is thought to be associated with increased nodal involvement and poor survival in patients with breast cancer. Overexpression of cyclooxygenase-2 (COX-2) in breast cancer is associated with indicators of poor prognosis such as lymph node metastasis, poor differentiation, and large tumor size. The underlying mechanism by which HPA and COX-2 overexpression increases the metastatic potential of breast cancer is not fully-understood. To enhance our understanding over these mechanisms, we aimed to investigate the relationship between the size of the tumor and HPA expression, tumor grade as well as lymph node status in patients with breast cancer. MATERIALS AND METHODS: Immunohistochemical analysis of HPA and COX-2 expression was performed on 246 breast tumor samples. The expression of HPA was correlated with COX-2 expression, tumor grade, lymph node status, oestrogen receptor status. RESULTS: The overexpression of HPA and COX-2 was associated with increased likelihood of lymph node positivity in large, high-grade tumors. High-grade tumors with size greater than 20 mm, that overexpressed HPA, were 4-times more likely to be associated with lymph node involvement (OR 4.71, CI 1.21-18.25). Whereas, tumors greater than 20 mm in size were 5-times more likely to metastasize to the regional lymph nodes, if associated with overexpression of COX-2 (OR 5.5, CI 1.2-24.8). CONCLUSION: Expression of HPA appears to be a key mechanism by which large, high-grade breast tumors metastasize to regional lymph nodes, while COX-2 overexpression may be an independent predictor of lymph node positivity.

Physical activity levels in women attending breast screening, receiving chemotherapy and post-breast cancer treatment; a cross-sectional study.

BACKGROUND: A lack of physical activity (PA) is a well-recognised risk factor in the development of breast cancer (BC) and evidence-base research on the impact of PA on BC survival is consolidating. However, evidence reveals that BC survivors have low levels of PA, suggesting the need of targeted interventions to enhance the PA behaviour of BC survivors. Unfortunately, there is lack of data from the UK about the PA behaviours of women at various stages of diagnosis and treatment of BC. Therefore, the aim of the present study was to assess PA levels in women at different stages of BC pathway. PATIENTS AND METHODS: A convenient sample of patients was selected at various stages of presentation and treatment of BC. Patients attending for breast screening for NHSBSP (n = 188), post-operative patients attending for chemotherapy (n = 41) and BC patients within one year's post-treatment (n = 80) were invited to take part in this cross-sectional study. RESULTS: Based on the odds ratio, the likelihood of a chemotherapy participant not meeting PA guidelines (i.e., being in the low activity category) were three times higher than the odds of a NHSBPS attendee not meeting PA guidelines, and compared to post-treatment participants, the chemotherapy patient's odds of not meeting PA guidelines was four times higher. The odds of NHSBPS attendees being in the high activity category compared to the moderate category were three times higher than that of a post-treatment participant. CONCLUSIONS: The current study suggests the need to establish robust PA interventions to enhance the PA behaviour of breast cancer survivors.

Endothelial dysfunction as a determinant of trastuzumab-mediated cardiotoxicity in patients with breast cancer.

BACKGROUND: Breast cancer is the most common cancer in females in the UK and has greater severity in patients who overexpress human epidermal growth receptor 2 (HER2) proteins in the breast tissue. Trastuzumab is a humanised monoclonal antibody and is targeted towards blocking the HER2 pathway and effectively reduces the recurrence of breast cancer and associated mortality. However, trastuzumab is also associated with an increased risk of cardiotoxicity which likely results from inhibition of the HER2 pathway. Under normal conditions HER2 pathways help maintain the integrity of the myocardial contractile elements, as well as the coronary vasculature, but trastuzumab inhibits these survival pathways and increases the risk for congestive heart failure (CHF). In the present review, we summarise the pathways that are implicated in the development of CHF in patients receiving trastuzumab. We also highlight the role of trastuzumab-mediated endothelial dysfunction and CHF.

Cancer cachexia prevention via physical exercise: molecular mechanisms.

Cancer cachexia is a debilitating consequence of disease progression, characterised by the significant weight loss through the catabolism of both skeletal muscle and adipose tissue, leading to a reduced mobility and muscle function, fatigue, impaired quality of life and ultimately death occurring with 25-30 % total body weight loss. Degradation of proteins and decreased protein synthesis contributes to catabolism of skeletal muscle, while the loss of adipose tissue results mainly from enhanced lipolysis. These mechanisms appear to be at least, in part, mediated by systemic inflammation. Exercise, by virtue of its anti-inflammatory effect, is shown to be effective at counteracting the muscle catabolism by increasing protein synthesis and reducing protein degradation, thus successfully improving muscle strength, physical function and quality of life in patients with non-cancer-related cachexia. Therefore, by implementing appropriate exercise interventions upon diagnosis and at various stages of treatment, it may be possible to reverse protein degradation, while increasing protein synthesis and lean body mass, thus counteracting the wasting seen in cachexia.

An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression.

BACKGROUND: Plants have proved to be an important source of anti-cancer drugs. Here we have investigated the cytotoxic action of an aqueous extract of Fagonia cretica, used widely as a herbal tea-based treatment for breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometric analysis of cells labeled with cyclin A, annexin V and propidium iodide, we describe a time and dose-dependent arrest of the cell cycle in G0/G1 phase of the cell cycle and apoptosis following extract treatment in MCF-7 (WT-p53) and MDA-MB-231 (mutant-p53) human breast cancer cell lines with a markedly reduced effect on primary human mammary epithelial cells. Analysis of p53 protein expression and of its downstream transcription targets, p21 and BAX, revealed a p53 associated growth arrest within 5 hours of extract treatment and apoptosis within 24 hours. DNA double strand breaks measured as γ-H2AX were detected early in both MCF-7 and MDA-MB-231 cells. However, loss of cell viability was only partly due to a p53-driven response; as MDA-MB-231 and p53-knockdown MCF-7 cells both underwent cell cycle arrest and death following extract treatment. p53-independent growth arrest and cytotoxicity following DNA damage has been previously ascribed to FOXO3a expression. Here, in MCF-7 and MDA-MB-231 cells, FOXO3a expression was increased significantly within 3 hours of extract treatment and FOXO3 siRNA reduced the extract-induced loss of cell viability in both cell lines. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate for the first time that an aqueous extract of Fagonia cretica can induce cell cycle arrest and apoptosis via p53-dependent and independent mechanisms, with activation of the DNA damage response. We also show that FOXO3a is required for activity in the absence of p53. Our findings indicate that Fagonia cretica aqueous extract contains potential anti-cancer agents acting either singly or in combination against breast cancer cell proliferation via DNA damage-induced FOXO3a and p53 expression.

Breast clinic and life style study BLLISS.

BACKGROUND: Independent, strong and unequivocal evidence suggests that life style factors such as obesity and lack of physical activity along with certain reproductive choices can increase the risk of breast cancer. There are no studies measuring the effectiveness of guidelines from the Department of Health regarding life style choices made by women presenting to breast clinics. The aim of this audit was to study the prevalence of obesity, physical activity and reproductive factors in women referred to breast clinic. PATIENTS AND METHODS: All patients attending the Breast clinic as new referrals were invited to complete a life style questionnaire. The data was analysed for prevalence of various risk factors for breast cancer. Three hundred and 73 patients completed the questionnaire. RESULTS: Final analyses of 373 patients demonstrated that 42% of women performed no exercise and only 24% of patients met Department of Health guideline of 30 minutes of exercise for 5 days a week. Overall 50% of patients were either obese or overweight and 22% of patients had BMI of > 30 kg/m2. The median age of menarche was 13 and 18% of women started their period below the age 12. Twenty one percent of women were nulliparous and 14% had their first live birth after the age of 30. Fourteen percent of patients were on the hormone replacement therapy of which 57% have used hormones for more than 5 years. Twenty two percent of women smoked and 9% of women consumed alcohol 5 days a week of which 13% had more than 4 glasses of alcohol in a day. CONCLUSION: There is preponderance of high risk life style choices in women attending breast clinic. If these life style options are not modified, there could potentially be a significant rise in the number of breast cancer in West Midlands.

Obesity in post menopausal women with a family history of breast cancer: prevalence and risk awareness.

BACKGROUND: Obesity and physical activity are modifiable risk factors in the development of post-menopausal breast cancer. The aim of this study was to assess the level of awareness and prevalence of these factors in women attending family history clinics. METHODS: Women attending the breast cancer family history clinic from 2004 to 2006 completed a questionnaire (SP15 format) about their knowledge of and exposure to various diet and lifestyle factors. All women had been counselled by a Consultant Cancer Geneticist and were given verbal and written information on the effect of life style on breast cancer risk. Responses were analysed using SPSStrade mark software. RESULTS: The response rate was 70% and two thirds of women were post-menopausal. The prevalence of obesity in post-menopausal women was 37% with 40% being overweight. The majority of women consumed a healthy balanced diet. Only 15% of post-menopausal women exercised for more than 4 hours per week. Two-thirds of women correctly stated that obesity increases their breast cancer risk and 73% of these were overweight or obese. Over 87% were correctly aware of the role of family history, 68% of a high fat diet, and 57% of hormone replacement therapy in the development of breast cancer. CONCLUSION: Women attending family history clinics lead a high risk lifestyle for the development of breast cancer with high prevalence of obesity and low levels of physical activity. A campaign of patient education is needed to promote healthy lifestyle choices, especially physical activity, in these high-risk women.